N-substituted aminomethanediphosphonic acids

Abstract

N-substituted aminomethanediphosphonic acids of the formula I, (* CHEMICAL STRUCTURE *) (I) wherein R1, X, alk1, R2 and n are as defined in the description, and salts thereof, have valuable pharmaceutical properties and are effective e.g. in the treatment of conditions which can be associated with disorders of the calcium metabolism. They are manufactured in a manner known per se.

I claim: 
     
       1. An N-substituted aminomethanediphosphonic acid of the formula I ##STR9## in which R 1  is an aromatic radical, X is oxy, thio, sulphinyl, sulphonyl or a covalent bond, alk 1  denotes a divalent aliphatic radical, R 2  is hydrogen or a monovalent aliphatic radical, n is 1, or a salt thereof. 
     
     
       2. A compound of the formula ##STR10## wherein R 1  is a phenyl or naphthyl radical which radical is unsubstituted or mono-, di- or tri-substituted by substituents selected from lower alkyl, lower alkoxy, lower alkylenedioxy, hydroxyl, halogen and trifluoromethyl, X is oxy, thio, sulphinyl, sulphonyl or a covalent bond, alk 1  is lower alkylene, R 2  is hydrogen, lower alkyl or lower alkenyl, n is 1, or a salt thereof. 
     
     
       3. A compound as claimed in claim 1 of the formula I wherein R 1  is a phenyl radical which is unsubstituted or mono- or disubstituted by substituents selected from C 1  -C 4  alkyl, C 1  -C 4  alkoxy, C 1  -C 4  alkylenedioxy, hydroxyl, halogen and trifluoromethyl, X is oxy, thio, sulphonyl or a covalent bond, alk 1  is C 2  -C 6  alkylene, R 2  is hydrogen or C 1  -C 4  alkyl, n is 1, or a salt thereof. 
     
     
       4. A compound as claimed in claim 1 of the formula I wherein R 1  is phenyl which is unsubstituted or substituted by C 1  -C 4  alkyl, C 1  -C 4  alkoxy, hydroxyl, halogen or trifluoromethyl, X is oxy, thio or a covalent bond, alk 1  is C 2  -C 4  alkylene, R 2  is hydrogen or C 1  -C 4  alkyl, n is 1, or a salt therof. 
     
     
       5. A compound as claimed in claim 1 of the formula I wherein R 1  is phenyl which is unsubstituted or substituted by C 1  -C 4  alkyl, C 1  -C 4  alkoxy, hydroxyl or halogen, X is oxy or thio, alk 1  is C 2  -C 4  alkylene, R 2  is hydrogen or C 1  -C 3  alkyl, and n represents 1, or a salt thereof. 
     
     
       6. N-(3-phenoxypropyl)-N-methyl-formamidinomethanediphosphonic acid according to claim 2 or a pharmaceutically acceptable salt thereof. 
     
     
       7. N-(2-phenylthioethyl)-N-methyl-formamidinomethanediphosphonic acid according to claim 2 or a pharmaceutically acceptable salt thereof. 
     
     
       8. N-(2-phenylethyl)-N-methyl-formamidinomethanediphosphonic acid according to claim 2 or a pharmaceutically acceptable salt thereof. 
     
     
       9. N-[3-(4-chlorophenoxy)propyl]-N-methyl-formamidinomethanediphosphonic acid according to claim 2 or a pharmaceutically acceptable salt thereof. 
     
     
       10. A pharmaceutical composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable carrier. 
     
     
       11. A method of treating conditions which can be associated with disorders of the calcium metabolism in mammals which comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of formula I according to claim 1, or a pharmaceutically acceptable salt thereof. 
     
     
       12. A pharmaceutical composition comprising a compound according to claim 2 and at least one pharmaceutically acceptable carrier. 
     
     
       13. A method of treating conditions which are associated with disorders of the calcium metabolism in mammals which comprises administering to a mammal in need thereof a therapeutically effective amount of a compound according to claim 2, or a pharmaceutically acceptable salt thereof.